The effect of spinal analgesia on visceral nociceptive neurons in caudal medulla of the rat.

UNLABELLED: A population of neurons resident in the caudal ventrolateral medulla are excited by noxious cutaneous and visceral stimuli from large portions of the body. These neurons act as monitors of ascending nociceptive information, and we hypothesized that they would be inhibited by spinally administered analgesics in a clinically relevant fashion. Rats were anesthetized with oxygen/ halothane. The caudal medulla was surgically exposed, and a catheter placed into the intrathecal space overlying the lower thoracic spinal cord via the surgical site. Single medullary neurons were characterized for responses to cutaneous and visceral (colorectal distension) stimuli. The effects of i.v. and intrathecally administered morphine and lidocaine were determined. The intrathecal infusion of morphine for 6 days before testing was also used as a pretreatment. Colorectal distension-evoked responses of medullary nociceptive neurons were inhibited in a dose-dependent, naloxonereversible fashion by intrathecal and i.v. morphine (50% effective dose values: 3.5 and 440 microg/kg, respectively). Intrathecal lidocaine abolished responses to colorectal distension and produced a spinal level at doses producing minimal effects when administered systemically. Prior treatment with an infusion of morphine produced tolerance to the effects of subsequent intrathecal morphine administration. These findings support the use of this preparation as a neurophysiologic model of spinal analgesia. IMPLICATIONS: Neurons in the brainstem, isolated electrophysiologically, were used as whole body monitors of pain-related activity in the rat. As a neurophysiologic model of nociception, this preparation may prove useful for the study of regionally administered analgesics and local anesthetics.

The effect of morphine on responses of nucleus ventroposterolateralis neurons to colorectal distension in the rat.

In 71 halothane-anesthetized rats, we characterized the responses of single neurons in the nucleus ventroposterolateralis (VPL) of the thalamus to a noxious visceral stimulus (colorectal balloon distension; CRD) and studied the effects of intravenous morphine on these responses using standard extracellular microelectrode recording techniques. One hundred nine neurons were isolated on the basis of spontaneous activity. Sixty-four (59%) responded to CRD, of which 52 (81 %) had excitatory and 12 (19%) had inhibitory responses. Neurons showed graded responses to graded CRD pressures (20-100 mmHg), with maximum excitation or inhibition occurring at 80 mmHg. Responses to noxious (pinch, heat) and innocuous (brush, tap) cutaneous stimuli were studied in 95 of the VPL neurons isolated. Eighty-three of these neurons (48 CRD responsive and 35 CRD nonresponsive) (87%) had cutaneous receptive fields, of which 96% were small and contralateral and 4% were large and contralateral or bilateral. Ninety-four percent of these neurons responded to both noxious and innocuous cutaneous stimulation, and 6% responded to only noxious stimulation. No neurons responded solely to innocuous stimulation. Cumulative doses of morphine (0.125, 0.25, 0.5, 1, and 2 mg/kg, i.v) produced statistically significant dose-dependent attenuation of neuronal responses to CRD. Naloxone (0.4 mg/ kg, i.v.) reversed the effects of morphine. Morphine and naloxone had no significant effects on spontaneous activity. These data support the involvement of VPL neurons in visceral nociception and are consistent with a role of VPL in sensory-discriminative aspects of nociception.

The effect of morphine on responses of mediodorsal thalamic nuclei and nucleus submedius neurons to colorectal distension in the rat.

In halothane-anesthetized rats, we characterized the responses of single neurons in the nuclei of medial thalamus (MT), specifically the mediodorsal thalamic nucleus (MD) and the nucleus submedius (Sm), to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine (Mor) on these responses using standard extracellular microelectrode recording techniques. 62 MD and 46 Sm neurons were isolated on the basis of spontaneous activity. 47 of the MD neurons (76%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. 38 of the Sm neurons (83%) responded to CRD, of which 89% had excitatory and 11% had inhibitory responses. Responses of MD and Sm neurons excited by CRD were related significantly to distension pressure (20-100 mmHg), with maximum excitation occurring at 60 and 100 mmHg, respectively. MD neurons inhibited by CRD also had graded responses to graded CRD, with maximum inhibition occurring at 80 mmHg. The responses to noxious (pinch, heat) and nonnoxious (tap, brush) cutaneous stimuli were studied in 59 of the MD and 44 of the Sm neurons isolated. 22 of the MD neurons (37%) studied had cutaneous receptive fields, of which 59% were large and bilateral, 41% were small and usually contralateral receptive fields. 55% of these neurons were nociceptive-specific, 45% responded to both noxious and nonnoxious cutaneous stimulation. 29 of the Sm neurons (66%) studied had cutaneous receptive fields, of which 72% were large and usually bilateral, 14% were small and bilateral, 14% were small and contralateral receptive fields. 90% of these neurons were nociceptive-specific, 10% responded to both noxious and nonnoxious stimulation. No MD or Sm neurons responded exclusively to nonnoxious cutaneous stimulation. Mor (0.125, 0.25, 0.5 and 1 mg/kg I.V.) attenuated MD and Sm neuronal excitatory responses to CRD in a dose-dependent fashion, abolishing evoked activity with a dose of 0.5 mg/kg (p < 0.05) and 1 mg/kg (p < 0.05), respectively. Naloxone (0.4 mg/kg I.V.) reversed the effects of Mor. Mor and naloxone had no effects on spontaneous activity. These data support the involvement of MD and Sm neurons in visceral nociception, and are consistent with a role of Sm in affective-motivational, and MD in both sensory-discriminative and affective-motivational aspects of nociception.

Hypoplastic internal carotid artery mimicking a classic angiographic "string sign". Case report.

The authors report the case of a patient with transient ischemic attacks who was evaluated by duplex scanning, which demonstrated total carotid artery occlusion. Arteriography revealed what appeared to be a classic "string sign" in the cervical carotid artery, and a standard endarterectomy was planned. At surgery the internal carotid artery was found to be congenitally atretic, accounting for the string appearance of the arteriogram. The etiology, associated anomalies, differential diagnosis, and diagnostic evaluation of such lesions are discussed.

Management strategies for tumors of the axis vertebra.

Primary and metastatic tumors of the axis vertebra pose difficult surgical problems. The authors report 14 cases of patients with axis tumors who underwent surgery between 1970 and 1993. The eight male and six female patients ranged in age from 9 to 70 years (mean 46 years). Presenting symptoms and signs included pain in 12, myelopathy in nine, radiculopathy in four, and cranial nerve deficits in two patients. Preoperative instability of the cervical spine was present in eight patients. The goal of surgery was to achieve diagnosis, decompression, and stabilization; the choice of operative intervention was based on tumor location and patient prognosis. Six transoral-transpalatal resections, two lateral extrapharyngeal approaches, four posterolateral decompressions, and 11 dorsal decompressions were performed. Eleven fusion procedures were required to achieve spinal stability. Patients with aggressive tumors requiring concomitant radiotherapy underwent fusion using contoured loop instrumentation or methyl methacrylate, whereas those with benign lesions underwent fusion using traditional techniques. With maximum medical and surgical intervention, 10 patients are alive and their tumors are in remission. In eight of these 10 patients, gross-total resection was achieved. Four patients died from tumor progression, and in three of these cases gross-total resection was not possible. There were no operative deaths and morbidity was minimal. Development of new surgical approaches to the axis has allowed resection of previously inoperable tumors. The extent of resection correlated with the duration of survival. A classification system for axis tumors is proposed to facilitate selection of appropriate surgical approaches that will maximize the extent of resection while achieving or maintaining spinal stability.

Pathogenesis and treatment of growing skull fractures.

BACKGROUND: Growing skull fractures are poorly understood complications of pediatric skull fractures. METHODS: A retrospective review of skull fractures at our institution from 1980-1993 revealed 10 patients with growing skull fractures. The age at injury ranged from 1-144 months, with 9 of 10 patients being under one year of age. The etiology of these fractures included falls, motor vehicle accidents, and child abuse. On average, growth of the fracture was diagnosed 14 months after the initial injury. RESULTS: Six patients have had magnetic resonance imaging (MRI) with one demonstrating leptomeningeal cyst herniation, two having brain herniation, and three having both brain parenchyma and leptomeningeal cyst herniation. All patients had malacic cortex underlying the fracture, but there was no evidence of intracranial hypertension. Nine patients have undergone craniotomy with excision of granulation tissue and gliotic brain, dural repair, and cranioplasty using surrounding normal skull. There were no surgical complications or recurrences. CONCLUSIONS: Brain/leptomeningeal cyst herniation through a dural rent, without MRI evidence of increased intracranial pressure, implicates physiologic growth and brain cerebrospinal fluid (CSF) pulsations as the cause of fracture enlargement.

Cervical epidural hematoma secondary to an extradural vascular malformation in an infant: case report.

We present a report of a 22-month-old infant with a spontaneous spinal epidural hematoma arising from a purely epidural vascular malformation. Although often suspected as a cause of spontaneous epidural hemorrhage, vascular malformations have rarely been demonstrated. The important aspects of the presenting symptoms in this young age group are highlighted. We discuss the entity of spontaneous epidural hemorrhage and the characteristics that distinguish purely epidural from dural arteriovenous malformations.

Perioperative management and surgical outcome of the acromegalic patient with sleep apnea.

Sleep apnea is a rare complicating factor of acromegaly associated with a high risk of perioperative airway compromise and unclear response to transsphenoidal resection of the underlying pituitary tumor. We reviewed four acromegalic patients with sleep apnea and documented postoperative objective and subjective improvement of their sleep disorders. The pathogenesis of this disorder and safe perioperative airway management are discussed.

Diagnosis of recurrent brain tumor: value of 201Tl SPECT vs 18F-fluorodeoxyglucose PET.

OBJECTIVE: This prospective study was designed to compare the sensitivity and specificity of a relatively simple examination, 201Tl chloride single-photon emission CT (SPECT), with a more complex examination, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), in patients thought to have recurrent brain tumor. Because both agents have been shown to be markers of viable tumor, we hypothesized that their sensitivity and specificity should be the same. SUBJECTS AND METHODS: Nineteen patients with evidence of recurrent tumor on CT or MR images were studied with both 201Tl SPECT and FDG PET imaging. Two patients were examined twice, so a total of 21 studies were evaluated. The 201Tl SPECT and FDG PET examinations were performed on the same day in 17 patients, and the remaining four examinations were done within 1 week of one another. Three reviewers independently interpreted each Tl SPECT and PET scan. Inappropriate regional increases in 201Tl or FDG activity were considered indicative of tumor recurrence. Sensitivity and specificity values were based on biopsy results and clinical follow-up. The final diagnosis was tumor recurrence in 16 cases and radiation necrosis in 5 cases. The relationship of scan results to survival was analyzed. RESULTS: The sensitivity and specificity of the 201Tl examination for detecting tumor recurrence were 11 (69%) of 16 and two (40%) of five, respectively; values for the FDG PET examination were 13 (81%) of 16 and 2 (40%) of 5, respectively. In patients with recurrent tumors less than 1.6 cm in size, results were false-negative in four 201Tl SPECT examinations and three FDG PET studies. All tumor lesions 1.6 cm or larger (n = 8) were detected. Agreement among the three nuclear medicine specialists was complete for each of the 201Tl SPECT scans. There was disagreement on the interpretation of five (24%) of the 21 FDG PET scans, which was resolved by consensus. Scintigraphic findings did not correlate with patients' survival times. CONCLUSION: We were unable to detect a statistically significant difference in sensitivity or specificity between the 201Tl SPECT and FDG PET scans. Both techniques were sensitive for tumor recurrence with lesions less than 1.6 cm or larger. However, given the greater availability, simplicity, and ease of interpretation and the lower cost of the 201Tl SPECT studies, this technique should be considered for detection of tumor recurrence with lesions that are demonstrated to be 1.6 cm or larger on CT or MR examinations.

Sphenoid wing meningioma progression after placement of a subcutaneous progesterone agonist contraceptive implant.

A causal relationship between sex steroids and meningioma proliferation has long been suspected. We report a case of the clinical progression of a sphenoid wing meningioma after the placement of Norplant, a subcutaneous contraceptive implant containing levonorgestrel, a progesterone agonist. Although not proof of causation, this observation lends further credence to the importance of progesterone receptors in the growth and possible treatment of meningiomas.

PIP: Reported is a female case study of a 40-year-old patient who 4 weeks previous had received a Norplant subcutaneous contraceptive implant. The patient presented at 4 weeks postimplant with blurred vision in her left eye. She further reported never having used hormonal contraceptives. Her vision continued to deteriorate over the next several months to 20/60 visual acuity. After examination by neuro-ophthalmologists at the University of Iowa Hospital and Clinics system, the following abnormalities in the left eye were reported: impaired color vision; a severely reduced critical flicker fusion rating (13 Hz); an abnormality in the temporal field (using Humphrey 30-2 program); and a 3 times greater light sensitivity. The fundus and the optic nerve heads appeared normal. Magnetic resonance imaging revealed a homogeneous mass along the medial sphenoid wing which continued into the left cavernous sinus and sella. Part of this mass crowded the left optic nerve opening (chiasm). During the subsequent 6 weeks, the patient's visual acuity continued to deteriorate to 20/100 despite removal of the Norplant implant. The tumor mass was surgically removed and pathologically examined. It was a meningothelial neoplasm and tested positive for progesterone receptors (125 fmol/mg of protein). It tested negative for estrogen receptors. Authors provide a discussion on the history of hormonal influence/agonist effects on meningiomas. The authors conclude that there is evidence which supports the theory that meningiomas may be subject to hormonal influence and may be stimulated by hormones to grow. They further conclude that their observations do not prove a cause-and-effect relationship and that further research is needed.

Perioperative choroidal hemorrhage at pars plana vitrectomy. A case-control study.

PURPOSE: Risk factors for choroidal hemorrhage during pars plana vitrectomy surgery are currently not well defined. The authors analyzed potential risk factors for perioperative choroidal hemorrhage at pars plana vitrectomy in a case-control study. METHODS: Of 683 consecutive vitrectomy procedures, 13 cases of choroidal hemorrhage were identified in the operative or immediate postoperative period. Fifty vitrectomy controls from the same period were randomly selected and were compared with the hemorrhage cases by univariate analysis with respect to various potential risk factors. RESULTS: The incidence of choroidal hemorrhage associated with vitrectomy was 1.9%. Statistically significant risks (P < or = 0.05) included: greater age (mean, 70.9 versus 52.1 years); elevated preoperative pressure (19.9 versus 13.0 mmHg); preoperative diagnosis of rhegmatogenous retinal detachment (relative risk, 8.1); aphakic or pseudophakic status (relative risk, 5.2); and scleral buckle procedure at vitrectomy (relative risk, 12.0). Eyes with previous ocular trauma and previous vitrectomy had a reduced risk of choroidal hemorrhage. The incidence of severe visual loss (final visual acuity < 5/200) did not differ significantly from controls. CONCLUSIONS: Significant risk factors for choroidal hemorrhage are identified in this study which may help to identify patients at increased risk for this complication. Good visual outcome is possible after choroidal hemorrhage at vitrectomy (69% with visual acuity > 5/200).

In vivo comparison of phenylephrine and phenylephrine oxazolidine instilled in the monkey eye.

The ocular and cardiovascular effects as well as aqueous humor and plasma concentrations of 10% phenylephrine HCl and 1% phenylephrine oxazolidine (prodrug) were compared in cynomolgus monkeys. A volume of 25 microliters of either drug was administered to one eye followed by blood pressure, pulse, and pupillary measurements at 10 min intervals up to 60 minutes. Careful slit lamp examinations of the anterior segment, indirect ophthalmoscopy of the vitreous and retina, and ERGs were performed at 60 minutes. Four plasma determinations of phenylephrine following administration of either drug were made between 5 and 60 minutes. Measurement of phenylephrine in aqueous humor was also determined at 60 minutes following all other measurements. The maximal pupillary dilation after administration of 1% prodrug (mean + s.d. = 4.4 + 0.5 mm, n = 12) was slightly greater than after administration of phenylephrine 10% (mean + s.d. = 3.9 + 0.8 mm, n = 12). The differences in pupillary diameter from 20 through 40 minutes were statistically greater for the prodrug. The greater pupillary diameter at the earlier times resulted in an onset of pupillary dilation approximately 15 minutes earlier for the 1% prodrug. There was no ocular toxicity from either drug. Neither drug resulted in any ERG changes compared to baseline. Significantly higher aqueous humor levels along with lower plasma levels were detected and found to be statistically different following administration of the 1% prodrug when compared to 10% phenylephrine.

Aqueous vs viscous phenylephrine. II. Mydriatic effects.

We performed four studies to determine whether there is a difference in the mydriatic effect of 2.5% aqueous vs 2.5% viscous phenylephrine hydrochloride solutions. The first study was performed under "room light" conditions, and the mean (+/- SD) dilation at one hour was 0.87 +/- 1.18 mm for the aqueous and 0.86 +/- 1.14 mm for the viscous solutions. The second study was performed in a darkened room, and the mean dilation at one hour was slightly greater than in room light but was still minimal (aqueous, 1.14 +/- 1.00 mm; viscous, 1.07 +/- 1.11 mm). In the third study, patients were pretreated with a topical anesthetic (0.5% proparacaine hydrochloride), and the mean one-hour dilation was approximately twice (aqueous, 2.30 +/- 0.81 mm; viscous, 2.41 +/- 0.88 mm) that found in patients who were not pretreated with proparacaine. In the fourth study, the two phenylephrine solutions were used in combination with 1% tropicamide, and the mean one-hour dilation was 3.8 +/- 0.82 mm for the aqueous and 3.8 +/- 0.98 mm for the viscous solutions. Our studies show that there is no difference in the mydriatic effect of 2.5% aqueous vs 2.5% viscous phenylephrine solutions when used alone or in combination with 0.5% proparacaine or 1% tropicamide.